Trisubstituted benzoic acid intermediates

ABSTRACT

Novel trisubstituted benzoic acid intermediates which are useful in the preparation of certain herbicidal 2-(2,3,4-trisubstituted benzoyl)-1,3-cyclohexanediones are described.

This is a continuation of application Ser. No. 07/386,649 filed July 31,1989, now abandoned, which is a divisional of application Ser. No.07/272,841, filed Nov. 18, 1988, now abandoned.

BACKGROUND OF THE INVENTION

Certain 2-(2'3'4'tri-substituted benzoyl)-1,3-cyclohexanedioneherbicides are described in U.S. Pat. No. 4,780,127, issued Oct. 25,1988, U.S. application Ser. No. 129,026, filed Dec. 4, 1987; and a U.S.application entitled 2-(2',3',4'-trisubstitutedbenzoyl)-1,3-cyclohexanediones, with William J. Michaely, Inventor,filed herewith, and all incorporated herein by reference.

The above-described herbicidal compounds can have the followingstructural formula ##STR1##

wherein R⁷ through R¹² are hydrogen or C₁ -C₄ alkyl; R¹ is C₁ -C₄ alkyl,C₁ -C₄ haloalkyl, CH₂ CH₂ --OCH₃, CH₂ CH₂ OC₂ H₅, CH₂ CH₂ SCH₃, or CH₂CH₂ SC₂ H₅ ; R² is C₁ -C₄ alkyl; and n is the integer 0 or 2.

These herbicides can be prepared by reacting a dione of the structuralformula ##STR2## wherein R⁷ through R¹² are as defined with a mole oftrisubstituted benzoyl chloride of the structural formula ##STR3##wherein n, R¹ and R² are as defined above.

DESCRIPTION OF THE INVENTION

This invention has several embodiments which are as follows:

Embodiment A relates to novel intermediate compounds having thestructural formula ##STR4## wherein R is C₁ -C₂ alkyl, preferablymethyl; formyl; cyano; carboxy; or --CO₂ R^(a) where R^(a) is C₁ -C₄alkyl, preferably ethyl; most preferably R is --CO₂ C₂ H₅.

Embodiment B relates to novel intermediate compounds having thestructural formula ##STR5## wherein R is C₁ -C₂ alkyl, preferablymethyl; formyl; cyano; carboxy or --CO₂ R^(a) wherein R^(a) is C₁ -C₄alkyl, preferably ethyl; most preferably R is --CO₂ C₂ H₅.

Embodiment C relates to novel intermediate compounds having thestructural formula ##STR6## wherein R is C₁ -C₂ alkyl, preferablymethyl; formyl; cyano; carboxy or --CO₂ R^(a) wherein R^(a) is C₁ -C₄alkyl, preferably ethyl, most preferably R is --CO₂ C₂ H₅ and R¹ is C₁-C₄ alkyl; preferably C₁ -C₂ alkyl; C₁ -C₄ haloalkyl; --CH₂ CH₂ OCH₃ ;--CH₂ CH₂ OC₂ H₅ ; --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅, with the provisothat when R is carboxy, then R¹ is --CH₂ CH₂ OCH₃ ; --CH₂ CH₂ OC₂ H₅ ;--CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅.

Embodiment D relates to novel intermediate compounds having thestructural formula ##STR7## wherein R is C₁ -C₂ alkyl, preferablymethyl; formyl; cyano; carboxy or --CO₂ R^(a) wherein R^(a) is C₁ -C₄alkyl, preferably ethyl, most preferably R is --CO₂ C₂ H₅ and R¹ is C₁-C₄ alkyl, preferably C₁ -C₂ alkyl; C₁ -C₄ haloalkyl; --CH₂ CH₂ OCH₃ ;--CH₂ CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅ with the provisothat when R is carboxy, then R¹ is --CH₂ CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅,--CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅, with the proviso that when R iscarboxy, then R¹ is --CH₂ CH₂ OCH₃ ; --CH₂ CH₂ OC₂ H₅ ; --CH₂ CH₂ SCH₃or --CH₂ CH₂ SC₂ H₅.

Embodiment E relates to novel intermediate compounds having thestructural formula ##STR8## wherein R is C₁ -C₂ alkyl, preferablymethyl; formyl; cyano; carboxy or --CO₂ R^(a) wherein R^(a) is C₁ -C₄alkyl, preferably ethyl, most preferably R is --CO₂ C₂ H₅ ; R¹ is C₁ -C₄alkyl; C₁ -C₄ haloalkyl; --CH₂ CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅, --CH₂ CH₂SCH₃ or --CH₂ CH₂ SC₂ H₅ and R² is C₁ -C₄ alkyl, preferably methyl,ethyl or n-propyl with the proviso that when R is carboxy, then R¹ is--CH₂ CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅.

Embodiment F relates to novel intermediate compounds having thestructural formula ##STR9## wherein R⁴ is --CH₂ CH₂ OCH₃, --CH₂ CH₂ OC₂H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅, preferably --CH₂ CH₂ OCH₃ or--CH₂ CH₂ OC₂ H₅ ; and R² is C₁ -C₄ alkyl, preferably methyl, ethyl orn-propyl.

Embodiment G relates to novel intermediate compounds having thestructural formula ##STR10## wherein X is hydroxy or chlorine; R³ is--CH₂ CH₂ OCH₃ or --CH₂ CH₂ CO₂ H₅ and R² is C₁ -C₄ alkyl, preferablymethyl, ethyl or n-propyl.

Embodiment H relates to novel intermediate compounds having thestructural formula ##STR11## wherein X is hydroxy or chlorine and R⁴ is--CH₂ CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃, or --CH₂ CH₂ SC₂ H₅,preferably --CH₂ CH₂ OCH₃ or --CH₂ CH₂ OC₂ H₅.

Embodiment I relates to novel intermediate compounds having thestructural formula ##STR12## wherein R^(a) is C₁ -C₄ alkyl, preferablyethyl, R⁵ is C₁ -C₄ alkyl; C₁ -C₄ haloalkyl; --CH₂ CH₂ OCH₃ or --CH₂ CH₂OC₂ H₅ ; preferably --CH₂ CH₂ OCH₃ or --CH₂ CH₂ OC₂ H₅ and R² is C₁ -C₄alkyl, preferably methyl, ethyl or n-propyl.

In embodiments A-E, the group R can also be trifluoromethyl.

The trisubstituted benzoic acid chloride intermediates are useful in thepreparation of the previously described herbicidal2-(2',3',4'-trisubstituted benzoyl)-1,3-cyclohexanediones.

The several intermediate compounds of this invention can be prepared bythe general method shown in the Figure of the next page with R, R¹, R²and R⁵ being as defined. The groups R^(X) and R^(Z) and C₁ -C₄ alkyl.##STR13##

Referring to the Figure, and particularly to Reaction Steps (A) through(J), consider the following:

Generally in Reaction Step (A), a mole amount of the 3-substitutedphenol is reacted with 2 moles of the brominating agent N-bromo C₁ -C₄alkylamine, preferably N-bromo tetra-butyl amine in a solvent such asmethylene chloride at a temperature between -70° C. to 25° C. After thisreaction, the free brominated phenol is formed by reaction with a strongacid such as HCl. The N-bromo C₁ -C₄ alkyl amine can be prepared by areaction of 2 moles of C₁ -C₄ alkyl amine and a mole of bromine in asolvent such as methylene chloride at low temperatures to yield one moleof N-bromo C₁ -C₄ alkyl amine. The final reaction product is recoveredby conventional techniques.

For Reaction Step (B), one mole of the dibromo-substituted phenolreaction product of Step (A) is reacted with an appropriate alkylatingagent such as a 2-chloroethyl ethyl ether, 2-chloroethyl methyl ether,2-chloroethyl methyl sulfide, 2-chloroethyl ethyl sulfide or C₁ -C₄alkylchloride along with a catalytic amount of potassium iodide and amole excess of a base such as potassium carbonate. Alkyl iodides such asmethyl iodide or ethyl iodide may also be used. In these cases thecatalytic potassium iodide is not needed and little or no heat isrequired. The reaction is run at 50° C. to 80° C. for 4 hours withagitation. The reaction product is recovered by conventional techniques.

For Reaction Step (C), the dibromo compound from Reaction Step (B) isreacted with an equal mole amount of a C₁ -C₄ alkyl mercaptan along witha mole excess of a base such as potassium carbonate in a solvent such asdimethylformamide. The reaction is run for several hours at atemperature between 50° C. to 100° C. with stirring under an inertatmosphere such as nitrogen. The desired reaction product is recoveredby conventional techniques.

Generally, in Reaction Step (D), a mole amount of the2-nitro-4-substituted phenol is monobrominated with a mole amount of thebrominating agent N-bromo-C₁ -C₄ -alkyl amine according to the generalprocedure described for Reaction Step (A). 3-hydroxy-4-nitrobenzoic acidis the least preferred reactant because it results in a less purepreparation of 2-bromo-3-hydroxy-4-nitrobenzoic acid. Preferably analkyl ester of 3-hydroxy-4-nitrobenzoic acid is used. The ester can beprepared by conventional synthesis using concentrated sulfuric acid in asolution of alkanol such as ethanol.

Reaction Step (E) is run using the general procedure of Step (B). Moleamounts of the phenol and the alkylating agent are used.

For Reaction Step (F) the procedure of Step (C) is used. Thedisplacement of the nitro group by the mercaptan is essentiallyquantitative and occurs at temperatures from 0° C. to 25° C.

For Reaction Step (G) a mole amount of the alkyl ester of2-bromo-4-alkylthio benzoic is oxidized with at least 3 moles of anoxidizing agent such as m-chloroperbenzoic acid in a suitable solventsuch as methylene chloride by stirring a solution of the reactants at20° to 100° C. The desired intermediate is recovered by conventionaltechniques. During this reaction step the alkylthio substituent isoxidized to the corresponding alkylsulfone.

For Reaction Step (H) a mole amount of the2-bromo-3-substituted-4-alkylthio ester or cyano compound is hydrolyzedwith a base such as sodium hydroxide to the corresponding2-bromo-3-substituted-4-alkylthio benzoic acid. The hydrolysis is run ina solvent such as an 80 percent methanol-water mixture. The reaction canbe run at 25°-100° C. with stirring. The desired product is recovered byconventional techniques.

For Reaction Step (J) when "R" is cyano or an ester group a mole amountof the appropriate 2-bromo-3-substituted-4-nitro compound is hydrolyzedwith a base such as sodium hydroxide to the corresponding2-bromo-3-substituted-4-nitro benzoic acid. The hydrolysis is run in asolvent such as an 80 percent methanol-water mixture. The reaction canbe run at 25°-100° C. with stirring. The desired product is recovered byconventional techniques. When "R" is formyl, methyl or ethyl, a moleamount of the appropriate 2-bromo-3-substituted-4-nitro compound isoxidized to the corresponding trisubstituted benzoic acid with an excessof an oxidizing agent such as potassium permanganate or sodiumhypochloride according to the known procedures.

For Reaction Step (K) the alkyl ester of the trisubstituted benzoic acidis converted to the trisubstituted benzoic acid by the hydrolysis steptaught in Reaction Step (H).

The intermediate benzoic acids described herein can easily be convertedto their respective acid chlorides and then to their acid cyanides, ifdesired, by the following two reactions. First, a mole of oxalylchloride and a catalytic amount of dimethylformamide in a suitablesolvent such as methylene chloride at a temperature of 20° to 40° C. for1 to 4 hours is heated with a mole of the intermediate benzoic acid. Thecorresponding benzoic acid cyanide can easily be prepared from thebenzoic acid chloride by reaction with cuprous cyanide at a temperatureof 50° to 220° C. for 1 to 2 hours.

The following series of examples teach the synthesis of representativeintermediate compounds of this invention. The structures of allcompounds of the examples and tables were verified by nuclear magneticresonance (NMR), infrared spectroscopy (IR) and mass spectroscopy (MS).

EXAMPLE 1 Ethyl 2,4-dibromo-3-hydroxybenzoate ##STR14##

Using a procedure similar to that described (D. E. Pearson, R. D. Wysongand C. V. Breder in J. Org. Chem. 32, 2358 [1967]), to a 1-liter, 3-neckflask equipped with a mechanical stirrer, a nitrogen inlet and apressure equalizing addition funnel was added 59 grams (g) of t-butylamine (0.8 mole) in 400 milliliters (ml) of methylene chloride. Thismixture was cooled to -65° C. with dry ice/isopropanol. To the cooledsolution was slowly added (1 hour) 64 grams (0.4 mole [m]) of brominediluted in 50 ml of methylene chloride. After the addition was complete,the mixture was stirred for 1 hour at approximately -60° C. Ethyl3-hydroxyenzoate (0.2 mole 33.2 grams) was added, in one portion, to thecooled reaction mixture. This mixture was allowed to warm to roomtemperature overnight. The white solid was filtered off and washed witha minimum amount of methylene chloride and converted to the free phenol(ethyl 2,4-dibromo-3-hydroxybenzoate) using 500 ml methylene chlorideand 400 ml of 2 Normal (N) hydrochloric acid. Gas chromatographyindicated the product (49 g) was 92% pure. This material was a viscousoil.

Additional compounds were prepared by the same procedure as described inExample 1 and are listed in Table 1.

                  TABLE 1                                                         ______________________________________                                         ##STR15##                                                                    R          Physical Constant (m.p. °C.)                                ______________________________________                                        CN         194-198                                                            CO.sub.2 CH.sub.3                                                                        74-75                                                              CO.sub.2 H 198-200                                                            CHO        135-136                                                            CF.sub.3   58-61                                                              ______________________________________                                    

EXAMPLE 2 Ethyl 2,4-dibromo-3-(2-methoxyethoxy) benzoate ##STR16##

The ethyl ester from Example 1 (32.4 g, 0.1 mole) was dissolved in 200ml of dimethyl formamide (DMF) and an excess of potassium carbonate(27.6 g, 0.2 mole) and 2-chloroethyl methyl ether (18.8 g, 0.2 mole)along with a catalytic amount of potassium iodide (4.8 g, 0.03 mole)were added. This reaction mixture was vigorously stirred and maintainedat 70° C. for 4 hours. Normal workup gave 31.8 g of ethyl2,4-dibromo-3-(2-methoxy-ethoxy) benzoate as an oil, 94% pure by gaschromatography. This ester would readily be hydrolyzed to its acid viathe method described in Example 7.

Additional compounds were prepared by the same procedure as described inExample 2 (except in those cases using an alkyl iodide, the potassiumiodide catalyst was omitted and little or no heat was required) and arelisted in Table 2.

                  TABLE 2                                                         ______________________________________                                         ##STR17##                                                                    R         R.sup.1    Physical Constant (m.p. °C.)                      ______________________________________                                        CO.sub.2 C.sub.2 H.sub.5                                                                CH.sub.3   oil                                                      CO.sub.2 C.sub.2 H.sub.5                                                                n-C.sub.3 H.sub.7                                                                        oil                                                      CO.sub.2 H                                                                              CH.sub.3   115-117                                                  CO.sub.2 C.sub.2 H.sub.5                                                                CH.sub.2 CH.sub.2 Br                                                                     oil                                                      CO.sub.2 H                                                                              n-C.sub.4 H.sub.9                                                                        112-115                                                  CO.sub.2 H                                                                              C.sub.2 H.sub.4 OC.sub.2 H.sub.5                                                         65-70                                                    CO.sub.2 H                                                                              C.sub.2 H.sub.4 SCH.sub.3                                                                oil                                                      CO.sub.2 C.sub.2 H.sub.5                                                                CH.sub.2 CF.sub.3                                                                        41-43                                                    CO.sub.2 H                                                                              CH.sub.2 CF.sub.3                                                                        135-138                                                  CO.sub.2 H                                                                              C.sub.2 H.sub.4 OCH.sub.3                                                                75-80                                                    CO.sub.2 C.sub.2 H.sub.5                                                                C.sub.2 H.sub.4 SCH.sub.3                                                                oil                                                      CO.sub.2 C.sub.2 H.sub.5                                                                n-C.sub.4 H.sub.9                                                                        oil                                                      ______________________________________                                    

EXAMPLE 3 Ethyl 2-bromo-3-(2-methoxyethoxy)-4-ethylthiobenzoate##STR18##

Ethyl 2,4-dibromo-3-(2-methoxyethoxy) benzoate (15.3 g, 0.04 mole) wasdissolved in 125 ml of DMF and potassium carbonate (13.8 g, 0.1 mole)and ethyl mercaptan (4 g, 0.064 mole) were added. This mixture washeated at 70° C., under nitrogen, with vigorous stirring, for 4 hours.Normal workup gave 14.3 g of crude product (82% desired product by gaschromatography), ethyl 1-bromo-3-(2-methoxyethoxy)-4-ethylthiobenzoateas a viscous oil. This ester could readily be hydrolyzed to its freeacid via the method described in Example 7. The crude ester was purifiedvia silica chromatography using ether/pentane to give 11.2 g of pureproduct as an oil. The above-prepared ester was hydrolyzed to thecorresponding acid according to the procedure described in Example 8.

Additional compounds were prepared by the same procedures as describedin Example 3 and are listed in Table 3.

                  TABLE 3                                                         ______________________________________                                         ##STR19##                                                                    R       R.sup.1    R.sup.2 Physical Constant (m.p. °C.)                ______________________________________                                        CO.sub.2 C.sub.2 H.sub.5                                                              C.sub.2 H.sub.5                                                                          C.sub.2 H.sub.5                                                                       51-53                                              CO.sub.2 H                                                                            C.sub.2 H.sub.5                                                                          C.sub.2 H.sub.5                                                                       112-115                                            CO.sub.2 C.sub.2 H.sub.5                                                              C.sub.2 H.sub.5                                                                           -n-C.sub.3 H.sub.7                                                                   oil                                                CO.sub.2 C.sub.2 H.sub.5                                                              CH.sub.3    -n-C.sub.3 H.sub.7                                                                   oil                                                CO.sub.2 H                                                                            C.sub.2 H.sub.5                                                                           -n-C.sub.3 H.sub.7                                                                   100-104                                            CO.sub.2 H                                                                            CH.sub.3    -n-C.sub.3 H.sub.7                                                                   135-138                                            CO.sub.2 C.sub.2 H.sub.5                                                               -n-C.sub.3 H.sub.7                                                                       -n-C.sub.3 H.sub.7                                                                   oil                                                CO.sub.2 H                                                                             -n-C.sub.3 H.sub.7                                                                      CH.sub.3                                                                              150-152                                            CO.sub.2 H                                                                             -n-C.sub.3 H.sub.7                                                                      C.sub.2 H.sub.5                                                                       107-110                                            CO.sub.2 C.sub. 2 H.sub.5                                                              -n-C.sub.3 H.sub.7                                                                      CH.sub.3                                                                              oil                                                CO.sub.2 C.sub.2 H.sub.5                                                              CH.sub.3   CH.sub.3                                                                              oil                                                CO.sub.2 H                                                                            CH.sub.3   CH.sub.3                                                                              165-167                                            CO.sub.2 C.sub.2 H.sub.5                                                              C.sub.2 H.sub.4 SCH.sub.3                                                                C.sub.2 H.sub.5                                                                       oil                                                CO.sub.2 C.sub.2 H.sub.5                                                              C.sub.2 H.sub.4 OCH.sub.3                                                                CH.sub.3                                                                              oil                                                CO.sub.2 C.sub.2 H.sub.5                                                              C.sub.2 H.sub.4 OC.sub.2 H.sub.5                                                         CH.sub.3                                                                              oil                                                CO.sub.2 C.sub.2 H.sub.5                                                              C.sub.2 H.sub.4 OCH.sub.3                                                                 -n-C.sub.3 H.sub.7                                                                   oil                                                ______________________________________                                    

EXAMPLE 4 Ethyl 2-bromo-3-hydroxy-4-nitrobenzoate ##STR20##

A 0.1 mole of the ethyl ester of 3-hydroxy-4-nitrobenzoic acid wasmonobrominated using the procedure described in Example 1, except onlyone equivalent of bromine and two equivalents of t-butyl amine wereused. This reaction yielded ethyl 2-bromo-3-hydroxy-4-nitrobenzoate in70.1% yield. It had a melting point of 58°-61° C.

The ethyl ester of 3-hydroxy-4-nitrobenzoic acid was prepared asfollows:

To 100 g of 3-hydroxy-4-nitrobenzoic acid in 300 ml of ethanol was added15 ml of concentrated sulfuric acid. This solution was refluxed for 3hours and then a Dean-Stark trap was attached and 100 ml ofethanol-water was distilled off. The reaction mixture was cooled andpoured onto 500 grams of ice. The resulting solid was collected,dissolved in 500 ml of ether and the ether solution was washed threetimes with 1% aqueous sodium bicarbonate. The ether layer was dried andconcentrated to give 103.8 g of pure ester.

EXAMPLE 5 Ethyl 2-bromo-3-(2-methoxyethoxy)-4-nitrobenzoate ##STR21##

Using a procedure similar to that of Example 2, 0.2 moles of ethyl2-bromo-3-hydroxy-4-nitrobenzoate and an excess of potassium carbonate(0.35 moles) and 2-chloroethyl methyl ether (0.35 moles) along with acatalytic amount of potassium iodide (7.2 g, 0.045 m) were combined with350 ml of dimethylformamide. After heating at 70° C. for 4 hours, normalworkup gave 0.187 moles of ethyl2-bromo-3-(2-methoxyethoxy)-4-nitrobenzoate as a viscous oil. This estercan be readily hydrolyzed to its acid using the procedure of Example 8.

Additional compounds were prepared by the same procedure as described inExample 5 and are listed in Table 4.

                  TABLE 4                                                         ______________________________________                                         ##STR22##                                                                    R         Physical Constant (m.p. °C.)                                 ______________________________________                                        CO.sub.2 H                                                                              63-68                                                               ______________________________________                                    

Ethyl 2-bromo-3-(2-methoxyethoxy)-4-ethylthiobenzoate ##STR23##

Using a procedure similar to that of Example 3, 0.1 mole of ethyl2-bromo-3-(2-methoxyethoxy)-4-nitrobenzoate and an excess of potassiumcarbonate (0.2 mole) and a slight excess of ethyl mercaptan (0.125 mole)were combined in 200 ml of dimethylformamide at 0° C., under nitrogen.The reaction was stirred overnight at room temperature. Normal workupgave the desired product in essentially quantitative yield. Thiscompound was compared to the product from Example 3 and they wereidentical by all spectroscopic and chromatographic comparisons.

EXAMPLE 7 Ethyl 2-bromo-3-(2-methoxyethoxy)-4-ethylsulfonyl benzoate##STR24##

The ester, ethyl 2-bromo-3-(2-methoxyethoxy)-4-ethylthiobenzoate fromExample 3 (12 g) was dissolved in 100 ml of methylene chloride and solidm-chloroperoxybenzoic acid (85% pure, 0.1 mole) was added slowly over aperiod of 2 hours. The crude reaction mixture was stirred overnight. Theexcess peracid was destroyed with sodium bisulfite (100 ml, 5%,solution). The organic layer was washed three times with base, dried,concentrated and chromatographed on silica gel (CH₂ Cl₂ /(C₂ H₅)₂ O) togive 8.3 grams of pure ethyl2-bromo-3-(2-methoxyethoxy)-4-ethylsulfonylbenzoate as a viscous oil.

Additional compounds were prepared by the same procedure as described inExample 7 and are listed in Table 5.

                  TABLE 5                                                         ______________________________________                                         ##STR25##                                                                    R.sup.b                                                                             R.sup.1    R.sup.2 Physical Constant (m.p. °C.)                  ______________________________________                                        C.sub.2 H.sub.5                                                                     C.sub.2 H.sub.5                                                                          C.sub.2 H.sub.5                                                                       oil                                                  C.sub.2 H.sub.5                                                                      -n-C.sub.3 H.sub.7                                                                      CH.sub.3                                                                              84-87                                                C.sub.2 H.sub.5                                                                     C.sub.2 H.sub.4 OCH.sub.3                                                                n-C.sub.3 H.sub.7                                                                     oil                                                  C.sub.2 H.sub.5                                                                     C.sub.2 H.sub.4 OCH.sub.3                                                                CH.sub.3                                                                              oil                                                  C.sub.2 H.sub.5                                                                      -n-C.sub.5 H.sub.11                                                                     C.sub.2 H.sub.5                                                                       58-59                                                C.sub.2 H.sub.5                                                                      -n-C.sub.4 H.sub.9                                                                      C.sub.2 H.sub.5                                                                       45-49                                                ______________________________________                                    

EXAMPLE 8 2-bromo-3-(2-methoxyethoxy)-4-ethylsulfonybenzoic acid##STR26##

To 7.26 g (0.02 mole) of the ethyl2-bromo-3-(2-methoxyethoxy)-4-ethylsulfonylbenzoate in 50 ml of 80%methanol/water was added 1.2 g (0.03 mole) of sodium hydroxide. Afterstirring at room temperature overnight, 100 ml of ether was added andthe organic phase was extracted three times with 50 ml of 1N NaOH. Thecombined base extracts were acidified and extracted three times withmethylene chloride. The methylene chloride was dried and concentrated toyield 6.6 grams of 2-bromo-3-(2-methoxy-ethoxy)-4-ethylsulfonylbenzoicacid as a viscous oil.

Additional compounds were prepared by the same procedure as described inExample 5 and are listed in Table 6.

                  TABLE 6                                                         ______________________________________                                         ##STR27##                                                                    R.sup.1     R.sup.2 Physical Constant (m.p. °C.)                       ______________________________________                                        C.sub.2 H.sub.5                                                                           C.sub.2 H.sub.5                                                                       oil                                                        -n-C.sub.3 H.sub.7                                                                       CH.sub.3                                                                              155-160                                                   CH.sub.3     -n-C.sub.3 H.sub.7                                                                   145-149                                                   CH.sub.3    CH.sub.3                                                                              130-135                                                   C.sub.2 H.sub.4 OCH.sub.3                                                                  -n-C.sub.3 H.sub.7                                                                   112-115                                                   C.sub.2 H.sub.4 OCH.sub.3                                                                 CH.sub.3                                                                              oil                                                       ______________________________________                                    

The above-described benzoic acids can be readily converted to their acidchlorides using oxalyl chloride and a catalytic amount ofdimethylformamide. These acid chlorides can be reacted with theabove-described 1,3-cyclohexanedione to prepare the above-describedherbicidal 2,3,4-trisubstituted benzoyl-1,3-cyclohexanediones accordingto the following two-step reaction:

The process proceeds via the production of an enol ester intermediate asshown in reaction (1). The final product is obtained by rearrangement ofthe enol ester as shown in reaction (2). The two reactions may beconducted as separate steps by isolation and recovery of the enol esterusing conventional techniques prior to conducting step (2), or byaddition of a cyanide source to the reaction medium after the formationof the enol ester, or in one step by inclusion of the cyanide source atthe start of reaction (1). ##STR28## wherein n and R¹, R² and R⁷ throughR¹² are as defined above and the moderate base is such as tri-C₁ -C₆alkylamine, pyridine, alkali metal carbonate or alkali metal phosphate.

Generally, in step (1) mole amounts of the dione and substituted benzoylchloride are used, along with a slight mole excess of a moderate base.The two reactants are combined in an organic solvent such asacetonitrile, methylene chloride, toluene, ethyl acetate ordimethylformamide. The base and benzoyl reactant preferably are added tothe reaction mixture with cooling. The mixture is stirred at 0° C.-50°C. until the reaction is substantially complete.

The reaction product is worked up by conventional techniques. ##STR29##wherein R¹, R² and R⁷ through R¹² are as defined above.

Generally, in step (2) a mole of the enol ester intermediate is reactedwith 1 to 4 moles of the base, preferably about 2 moles of moderate baseand from 0.01 mole to about 0.5 mole or higher, preferably around 0.1mole of the cyanide source (e.g., potassium cyanide or acetonecyanohydrin). The mixture is stirred in a reaction pot until therearrangement is substantially complete at a temperature below 80° C.,preferably about 20° C. to about 40° C., and the desired product isrecovered by conventional techniques.

The term "cyanide source" refers to a substance or substances whichunder the rearrangement conditions consists of or generates hydrogencyanide and/or cyanide anion.

The process is conducted in the presence of a catalytic amount of asource of cyanide anion and/or hydrogen cyanide, together with a molarexcess, with respect to the enol ester, of a moderate base.

Preferred cyanide sources are alkali metal cyanides such as sodium andpotassium cyanide; cyanohydrins of methyl alkyl ketones having from 1-4carbon atoms in the alkyl groups, such as acetone or methyl isobutylketone cyanohydrins; cyanohydrins of benzaldehyde or of C₂ -C₅ aliphaticaldehydes such as acetaldehyde, propionaldehyde, etc., cyanohydrins;zinc cyanide; and hydrogen cyanide itself. Hydrogen cyanide isconsidered most advantageous as it produces relatively rapid reactionand is inexpensive. Among cyanohydrins the preferred cyanide source isacetone cyanohydrin.

The cyanide source is used in an amount up to about 50 mole % based onthe enol ester. It may be used in as little as about 1 mole % to producean aceptable rate of reaction at about 40° C. on a small scale. Largerscale reactions give more reproducible results with slightly highercatalyst levels of about 2 mole %. Generally about 1-10 mole % of thecyanide source is preferred.

The process is conducted with a molar excess, with respect to the enolester, of a moderate base. By the term "moderate base" is meant asubstance which acts as a base yet whose strength or activity as a baselies between that of strong bases such as hydroxides (which could causehydrolysis of the enol ester) and that of weak bases such asbicarbonates (which would not function effectively). Moderate basessuitable for use in this embodiment include both organic bases such astertiary amines and inorganic bases such as alkali metal carbonates andphosphates. Suitable tertiary amines include trialkylamines such astriethylamine, trialkanolamines such as triethanolamine, and pyridine.Suitable inorganic bases include potassium carbonate and trisodiumphosphate.

The base is used in an amount of from about 1 to about 4 moles per moleof enol ester, preferably about 2 moles per mole.

When the cyanide source is an alkali metal cyanide, particularlypotassium cyanide, a phase transfer catalyst may be included in thereaction. Particularly suitable phase transfer catalysts are the Crownethers.

A number of different solvents may be usable in this process, dependingon the nature of the acid chloride or the acylated product. A preferredsolvent for this reaction is 1,2-dichloroethane. Other solvents whichmay be employed depending on the reactants or products include toluene,acetonitrile, methylene chloride, ethyl acetate, dimethylformamide, andmethyl isobutyl ketone (MIBK).

In general, depending on the nature of the reactants and the cyanidesource, the rearrangement may be conducted at temperatures up to about50° C.

What is claimed is:
 1. A compound having the structural formula##STR30## wherein R is C₁ -C₂ alkyl, formyl, cyano, carboxy or CO₂ R^(a)wherein R^(a) is C₁ -C₄ alkyl and R₁ is C₁ -C₄ haloalkyl, --CH₂ CH₂OCH₃, --CH₂ CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅, with theproviso that when R is carboxy, then R₁ is --CH₂ CH₂ OCH₃ ; --CH₂ CH₂OC₂ H₅ ; --CH₂ CH₂ SCH₃ or CH₂ CH₂ SC₂ H₅.
 2. The compound of claim 1wherein R is carboethoxy or carboxy and R¹ is C₁ -C₄ alkyl, --CH₂ CH₂OCH₃, --CH₂ CH₂ OC₂ H₅, or --CH₂ CH₂ SCH₃.
 3. The compound of claim 1wherein R is carboethoxy and R¹ is --CH₂ CH₂ OCH₃.
 4. A compound of thestructural formula ##STR31## wherein R is C₁ -C₂ alkyl, formyl, cyano,carboxy or --CO₂ R^(a) wherein R^(a) is C₁ -C₄ alkyl, R¹ is C₁ -C₄haloalkyl; --CH₂ CH₂ OCH₃ ; --CH₂ CH₂ OC₂ H₅ ; --CH₂ CH₂ SCH₃ ; --CH₂CH₂ SC₂ H₅ with the proviso that when R is carboxy, then R¹ is only--CH₂ CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅. 5.The compound of claim 4 wherein R is carboethoxy and R¹ is --CH₂ CH₂OCH₃.
 6. A compound having the structural formula ##STR32## wherein R ismethyl, ethyl, formyl, cyano, carboxy or --CO₂ R^(a) wherein R^(a) is C₁-C₄ alkyl; R¹ is C₁ -C₄ alkyl, C₁ -C₄ haloalkyl, --CH₂ CH₂ OCH₃, --CH₂CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅ and R² is C₁ -C₄ alkylwith the proviso that when R is carboxy, then R¹ is only --CH₂ CH₂ OCH₃,--CH₂ CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅.
 7. The compound ofclaim 6 wherein R is carboethoxy or carboxy, R¹ is C₁ -C₄ alkyl, --CH₂CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅ or --CH₂ CH₂ --SCH₃ ; and R² is C₁ -C₄ alkyl.8. The compound of the structural formula ##STR33## wherein R⁴ is --CH₂CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅ and R² isC₁ -C₄ alkyl.
 9. The compound of claim 8 wherein R⁴ is --CH₂ CH₂ OCH₃and R² is C₁ -C₄ alkyl.
 10. A compound having the structural formula##STR34## wherein R³ is --CH₂ CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅, X is hydroxyor chlorine; and R² is C₁ -C₄ alkyl.
 11. The compound of claim 10wherein X is hydroxy or chlorine; R³ is --CH₂ CH₂ OCH₃, and R² is C₁ -C₄alkyl.
 12. The compound of claim 10 wherein X is chlorine.
 13. Thecompound of claim 10 wherein X is hydroxy.
 14. A compound of thestructural formula ##STR35## wherein X is hydroxy or chlorine; R⁴ is--CH₂ CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅.15. The compound of claim 14 wherein X is chlorine and R⁴ is --CH₂ CH₂OCH₃ or --CH₂ CH₂ OC₂ H₅.
 16. The compound of claim 14 wherein X ishydroxy and R⁴ is --CH₂ CH₂ OCH₃ or --CH₂ CH₂ OC₂ H₅.
 17. A compound ofthe structural formula ##STR36## wherein R^(a) is C₁ -C₄ alkyl, R¹ is C₁-C₄ alkyl; C₁ -C₄ haloakyl; --CH₂ CH₂ OCH₃ ; --CH₂ CH₂ OC₂ H₅ ; and R²is C₁ -C₄ alkyl.
 18. The compound of claim 17 wherein R^(a) is ethyl; R¹is --CH₂ CH₂ OCH₃ ; or --CH₂ CH₂ OC₂ H₅ and R² is C₁ -C₃ alkyl.